1. Field of the Invention
This invention relates to an anti-asthmatic agent, a method for the treatment of asthma, a pharmaceutical composition for the treatment of asthma and a process for preparing the pharmaceutical composition.
2. Description of the Prior Art
Asthma is a disease marked by paroxysmal dyspnea and stridor, which is caused by airway stenosis.
Typical causes of airway stenosis are constriction of airway smooth muscle, formation of edema in airway mucous membrane, exasperation of airway discharge and formation of mucocele in airway, among which the most important is the constriction of airway smooth muscle.
An asthma patient generally has an elethitic airway, which is liable to produce IgE antibody against many antigens including inhaled allergen. Therefore, asthma patients carry a large quantity of IgE antibody in their bodies, and if they inhale antigens such as pollen and the other allergens, and antigen-antibody reaction is liable to take place at the surface of mast cell existing abundantly in airway submucosa, and the release of histamine and SRS-A, (slow reacting substance of anaphylaxis), is triggered by the reaction, which causes asthma symptoms including the constriction of the smooth muscle (Progress in Medicing, Vol. 3, pages 655-666, 1983 published by Life Science K.K. Japan).
The spasm of bronchial smooth muscle by histamine is very sensitive, evanescent and strong, and serious paroxysm is over within a comparatively short time (Allergy, Vol. 7 pages 93-104, 1958.
In contrast, the constriction of bronchial smooth muscle by SRS-A occurs slowly, but continuously and strongly for a long period of time, which causes serious pain to the asthma patient. Therefore, the development of a medicine which can effectively inhibit the release of SRS-A has been desired (Progress in Medicine, Vol. 3, pages 655-666, 1983).
SRS-A is released from mast cells, or the like, by an antigen-antibody reaction in which an IgE antibody participates. Unlike histamine belonging to a preformed mediator, SRS-A is synthesized by the stimulation of the reaction and belongs to a newly generated mediator essentially consisting of leucotrienes C.sub.4, D.sub.4, E.sub.4 (LTC.sub.4, LTD.sub.4, LTE.sub.4) which are formed by a series of reactions, including the reaction of arachidonic acid initiated by 5-lipoxygenase, and whose chemical structures have been clarified (Meneki Yakuri, Immunology and Pharmacology), Vol 2, No. 2, pages 207-213, 1984).
As disclosed in Japanese Patent Public Disclosure No. 11975/1982, 5-(3-n-butyloxalyl-aminophenyl) tetrazole (MTB) is a compound which was synthesized in the Research Division of the Company in which the applicants are employed and was found to show an anti-allergic action. The compound has the following chemical formula. ##STR1##
Although it is known that MTB has an anti-allergic action, inhibiting the release of histamine, it has not been known that MTB has excellent SRS-A release-inhibiting action (Japanese Journal of Pharmacology, Vol. 32, pages 689-697, 1982).